Piperidine → 3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one

HRID 2191522Notes

Reaction equation

HRID 2191522 reaction equation
C(N(CC)CC[N:6]1[CH2:12][CH2:11][CH2:10][C:9]2[NH:13][C:14](C=O)=[C:15]([CH3:16])[C:8]=2[C:7]1=[O:19])C.FC1C(F)=CC=CC=1C1C(F)=CC=C2C=1CC(=O)N2.N1CCCCC1>C(O)C>[CH3:16][C:15]1[C:8]2[C:7](=[O:19])[NH:6][CH2:12][CH2:11][CH2:10][C:9]=2[NH:13][CH:14]=1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 592500644-(2,3-Difluoro-phenyl)-5-fluoro-1,3-dihydro-indol-2-oneHCID 592500815-(2-Diethylamino-ethyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde

Product 1

HCID 867021093-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-oneYield 56%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

5-(2-Diethylamino-ethyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 1j (73 mg, 0.25 mmol) and 4-(2,3-difluoro-phenyl)-5-fluoro-1,3-dihydro-indol-2-one 74 g (60 mg, 0.23 mmol) were dissolved in 2 ml of ethanol, and added with 35 μl of piperidine to the solution at room temperature. Upon completion of the addition, the mixture was heated to reflux for 2 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was naturally cooled to room temperature, and filtered. The filter cake was washed with anhydrous ethanol (3 ml×2) and dried to obtain the title compound (Z)-5-(2-(diethylamino)ethyl)-2-(4-(2,3-difluorophenyl)-5-fluoro-2-oxoindolin-3-ylidene)methyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 74 (23 mg, yield 19%) as an orange solid.

Workup

  1. additionUpon completion of the addition
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 2 hours
  4. filtrationfiltered
  5. washThe filter cake was washed with anhydrous ethanol (3 ml×2)
  6. customdried

Sources & evidence

ORD record
ord-32f28c922714404db8ccddc9de565f8a
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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